How Reading Our Genes May Transform Health Care

Having mapped all of the 3 billion characters in the human genome, including 20,000-plus human genes, a consortium of international researchers declared the Human Genome Project a success in 2003. But for researchers pursuing genomic medicine—the science of predicting disease risk and tailoring treatments based on an individual’s genetic makeup—the work had just begun. For all its potential, genomic medicine, or as Johns Hopkins researchers have taken to calling the field, individualized health, is still in its infancy.

As that research moves forward, the promise of this new, genome-based approach to medical therapy becomes easier to grasp. With a simple swab DNA test, for example, a woman already can learn whether or not she’s at higher risk for breast cancer. That knowledge might prompt her to seek more aggressive treatment at an earlier stage of detection. Two people with colon cancer may soon receive vastly different drug treatments depending on the pattern of changes in their tumor cells, allowing the correct allocation of treatments that will optimize efficacy while minimizing side effects. And a man with genetic indicators for heart disease might be advised earlier about lifestyle changes to prevent complications.

Perhaps most importantly—and this is fast becoming the holy grail of health care reform—individualized health could significantly reduce health care costs as doctors eliminate expensive treatments that can be shown through genetic profiling to be unhelpful or unnecessary. Public health experts say that billions of dollars are spent annually on medical treatments that are either uncalled for or that ultimately prove ineffective. But current medical understanding makes it extremely difficult to know in advance if a specific treatment will work well, or at all, for a specific individual. “Right now as physicians we treat an aggregate. We tell people, ‘An aspirin a day is good for you,’” explains Lloyd Minor, provost and senior vice president for academic affairs and an otolaryngologist. “But does everyone really benefit from that?”

Although individualized health has its advantages, all the information that comes with genetic screening presents weighty ethical questions. Emory University anesthesiologist Anne Marie McKenzie-Brown, Med ’87, came to understand some of those complications during the Johns Hopkins Volunteer Summit in October 2010, a gathering of over 350 Johns Hopkins leaders examining challenges facing the university. As the panel session on individualized health began, McKenzie-Brown believed that she would want to learn as much as she could from her own gene sequencing, even if it revealed risks of diseases for which no treatments or cures are known.

“I thought I’d want to know everything; I’m a physician, I believe in knowledge and information,” McKenzie-Brown remembers. “But we had such an honest, lively discussion. People shared their experiences with cancer, their different perspectives on the treatability of certain diseases. I was surprised by how much it changed my perspective.”

McKenzie-Brown and other participants at the individualized health discussion heard from Ruth Faden, director of the university’s Berman Institute of Bioethics, about how the internationally renowned institute is researching the difficult ethical dilemmas that the new science will present to patients and providers alike. “Say you had a high chance of contracting a debilitating disease for which there is no known cure,” explains McKenzie-Brown. “How does that affect your decisions on how to live your life, whether to marry, whether or not to have children—all in the face of a disease that you may or may not actually get? How would such knowledge affect your quality of life? You’re young—does this information affect your ability to get insurance? It raises all these questions. On the other hand, there’s the tremendous potential for advances in medical science. The possibility that we could achieve greater efficacy in treating disease and lower the risk of side effects is incredibly appealing.”

To reach that potential, dozens of Johns Hopkins researchers are working across disciplines on the individualized health puzzle. Ultimately, individualized health is more than genomic medicine. Its real power comes from combining genomic information with other clinical information such as blood pressure, weight, findings on imaging studies, and other observed data to select the best treatment—and even more importantly, the best disease prevention strategies—for each individual. Notes Minor, “This effort is broader than just the field of medicine because it addresses overall health, and advances will lead to strategies for preventing disease and improving health.”

One researcher leading the charge is Vasan Yegnasubramanian, Med ’06, who has a primary appointment in Oncology and a joint appointment in Environmental Health Sciences at Johns Hopkins. At the Next Generation Sequencing Center, he directs research that harnesses powerful advances in sequencing—enabled by a confluence of advances in engineering, imaging, molecular biology, biochemistry, and computational biology—in order to study the mechanisms linking environmental exposure, inflammation, and genetic/epigenetic alterations to cancer risk. “The ultimate goal is to harness new genomics technologies to craft rational strategies to target an individual’s tumor effectively,” Yegnasubramanian says. “It’s a major shift in how we treat cancer. Currently, we essentially use the same therapeutic strategy for all individuals presenting with a specific cancer type, despite knowing that only a fraction of those individuals may receive benefit from this one-size-fits-all approach. The new paradigm would allow us to rationally allocate medical therapies based on the genetic makeup of an individual’s disease, thereby allowing maximal efficacy while avoiding unnecessary side effects.”

The greatest hurdle facing researchers is how to collect and analyze vast amounts of data on genomic sequencing, disease progression, and treatment. The price of sequencing genes is falling quickly to the range of a simple blood test, making such tests increasingly accessible. Yet one individual’s complete genetic information comprises millions of bytes of data, posing challenges for computing power and storage capacity. Even Johns Hopkins astronomy faculty members have been drawn into the individualized health work, Minor says, because by hosting the Hubble telescope, those researchers have pioneered the handling and storing of enormous quantities of data.

Johns Hopkins is well-positioned to lead this medical transformation, Yegnasubramanian believes, because the work requires the convergence of high-level technology, cutting-edge biomedical research, and elite medical expertise. “Other universities are doing similar genome work, but they are often not tied closely to a hospital. At Hopkins we have a long history of clinicians working side by side with researchers and can really tackle this challenge from a multidisciplinary perspective.”

Last year’s Volunteer Summit highlighted not only the exciting potential of individualized health but, equally, the transformative nature of new research relationships evolving across university divisions. Says Minor, “The structure of academic institutions, with their individual schools and departments, was created 100 years ago. Some of that still makes sense. But our society looks to universities for guidance on increasingly complex problems that don’t fit in neat silos. If we’re going to continue to meet society’s needs, we have to look at new ways to bring our greatest resource—our faculty—together.”

For Yegnasubramanian and others involved in charting the new course of 21st-century medicine, the possibilities are enormous—and the payoff potentially immense. “We’re at the very early days, just at the envisioning stage,” he says, yet the advances energize him. “We have to be very cautious. We don’t want to hype up expectations and underdeliver. At the same time, I can’t contain my excitement at the prospects ahead.”